tbuckley/cabot-search huggingface dataset:
Effect of Disposable Elevator Cap Duodenoscopes on Persistent Microbial Contamination and Technical Performance of Endoscopic Retrograde Cholangiopancreatography
Authors: Nauzer Forbes, B. Joseph Elmunzer, Thibault Allain, Michael D. Parkins, Prameet M. Sheth, Barbara J. Waddell, Kristine Du, Katya Douchant, Olajumoke Oladipo, April Saleem, Shane Cartwright, Millie Chau, Megan Howarth, Jackie McKay, Tamim Nashad, Yibing Ruan, Kirles Bishay, Emmanuel Gonzalez-Moreno, Zhao Wu Meng, Sydney Bass, Robert Bechara, Martin J. Cole, Diederick W. Jalink, Rachid Mohamed, Christian Turbide, Paul J. Belletrutti, Ahmed Kayal, Puja R. Kumar, Robert J. Hilsden, André G. Buret, Lawrence Hookey, Steven J. Heitman
Journal: JAMA Internal Medicine (2023)

Importance Infection transmission following endoscopic retrograde cholangiopancreatography (ERCP) can occur due to persistent contamination of duodenoscopes despite high-level disinfection to completely eliminate microorganisms on the instrument. Objective To determine (1) contamination rates after high-level disinfection and (2) technical performance of duodenoscopes with disposable elevator caps compared with those with standard designs. Design, Setting, and Participants In this parallel-arm multicenter randomized clinical trial at 2 tertiary ERCP centers in Canada, all patients 18 years and older and undergoing ERCP for any indication were eligible. Intervention The intervention was use of duodenoscopes with disposable elevator caps compared with duodenoscopes with a standard design. Main Outcomes and Measures Coprimary outcomes were persistent microbial contamination of the duodenoscope elevator or channel, defined as growth of at least 10 colony-forming units of any organism or any growth of gram-negative bacteria following high-level disinfection (superiority outcome), and technical success of ERCP according to a priori criteria (noninferiority outcome with an a priori noninferiority margin of 7%), assessed by blinded reviewers. Results From December 2019 to February 2022, 518 patients were enrolled (259 disposable elevator cap duodenoscopes, 259 standard duodenoscopes). Patients had a mean (SD) age of 60.7 (17.0) years and 258 (49.8%) were female. No significant differences were observed between study groups, including in ERCP difficulty. Persistent microbial contamination was detected in 11.2% (24 of 214) of standard duodenoscopes and 3.8% (8 of 208) of disposable elevator cap duodenoscopes ( P = .004), corresponding to a relative risk of 0.34 (95% CI, 0.16-0.75) and number needed to treat of 13.6 (95% CI, 8.1-42.7) to avoid persistent contamination. Technical success using the disposable cap scope was noninferior to that of the standard scope (94.6% vs 90.7%, P = .13). There were no differences between study groups in adverse events and other secondary outcomes. Conclusions and Relevance In this randomized clinical trial, disposable elevator cap duodenoscopes exhibited reduced contamination following high-level disinfection compared with standard scope designs, without affecting the technical performance and safety of ERCP. Trial Registration ClinicalTrials.gov Identifier: NCT04040504
Disparities in Wait Times for Care Among US Veterans by Race and Ethnicity
Authors: Deborah Gurewich, Erin Beilstein-Wedel, Michael Shwartz, Heather Davila, Amy K. Rosen
Journal: JAMA Network Open (2023)

Importance Prior studies indicate that Black and Hispanic vs White veterans wait longer for care. However, these studies do not capture the COVID-19 pandemic, which caused care access disruptions, nor implementation of the US Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks Act (MISSION), which is intended to improve care access by increasing veterans’ options to use community clinicians. Objective To determine whether wait times increased differentially for Black and Hispanic compared with White veterans from the pre–COVID-19 to COVID-19 periods given concurrent MISSION implementation. Design, Setting, and Participants This cross-sectional study used data from the VA’s Corporate Data Warehouse for fiscal years 2019 to 2021 (October 1, 2018, to September 30, 2021). Participants included Black, Hispanic, and White veterans with a new consultation for outpatient cardiology and/or orthopedic services during the study period. Multivariable mixed-effects models were used to estimate individual-level adjusted wait times and a likelihood ratio test of the significance of wait time disparity change over time. Main Outcomes and Measures Overall mean wait times and facility-level adjusted relative mean wait time ratios. Results The study included 1 162 148 veterans (mean [SD] age, 63.4 [14.4] years; 80.8% men). Significant wait time disparities were evident for orthopedic services (eg, Black veterans had wait times 2.09 [95% CI, 1.57-2.61] days longer than those for White veterans) in the pre–COVID-19 period, but not for cardiology services. Mean wait times increased from the pre–COVID-19 to COVID-19 periods for both services for all 3 racial and ethnic groups (eg, Hispanic wait times for cardiology services increased 5.09 [95% CI, 3.62-6.55] days). Wait time disparities for Black veterans (4.10 [95% CI, 2.44-5.19] days) and Hispanic veterans (4.40 [95% CI, 2.76-6.05] days) vs White veterans (3.75 [95% CI, 2.30-5.19] days) increased significantly from the pre–COVID-19 to COVID-19 periods ( P &amp;amp;lt; .001). During the COVID-19 period, significant disparities were evident for orthopedic services (eg, mean wait times for Hispanic vs White veterans were 1.98 [95% CI, 1.32-2.64] days longer) but not for cardiology services. Although there was variation in wait time ratios across the 140 facilities, only 6 facility wait time ratios were significant during the pre–COVID-19 period and 26 during the COVID-19 period. Conclusions and Relevance These findings suggest that wait time disparities increased from the pre–COVID-19 to COVID-19 periods, especially for orthopedic services for both Black and Hispanic veterans, despite MISSION’s goal to improve access. Facility-level analyses identified potential sites that could be targeted to reduce disparities.
COVID-19 Vaccines in Young Children—Reassuring Evidence for Parents
Authors: Paul A. Offit
Journal: JAMA Pediatrics (2023)

Atsuyuki Watanabe, MD; Ryoma Kani; Masao Iwagami, MD, PhD; Hisato Takagi, MD, PhD; Jun Yasuhara, MD; Toshiki Kuno, MD, PhD
Assessment of Efficacy and Safety of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years
Authors: Atsuyuki Watanabe, Ryoma Kani, Masao Iwagami, Hisato Takagi, Jun Yasuhara, Toshiki Kuno
Journal: JAMA Pediatrics (2023)

Evidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers.To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis.PubMed and Embase databases were searched on September 29, 2022, without language restrictions.Randomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included.Two investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines.The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated.Two randomized clinical trials and 15 observational studies involving 10 935 541 vaccinated children (median or mean age range, 8.0-9.5 years) and 2 635 251 unvaccinated children (median or mean age range, 7.0-9.5 years) were included. Two-dose mRNA COVID-19 vaccination compared with no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47; 95% CI, 0.35-0.64), symptomatic SARS-CoV-2 infections (OR, 0.53; 95% CI, 0.41-0.70), hospitalizations (OR, 0.32; 95% CI, 0.15-0.68), and multisystem inflammatory syndrome in children (OR, 0.05; 95% CI, 0.02-0.10). Two randomized clinical trials and 5 observational studies investigated AEs among vaccinated children. Most vaccinated children experienced at least 1 local AE following the first injection (32 494 of 55 959 [86.3%]) and second injection (28 135 of 46 447 [86.3%]). Vaccination was associated with a higher risk of any AEs compared with placebo (OR, 1.92; 95% CI, 1.26-2.91). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4%-14.2%) and that of myocarditis was estimated to be 1.8 per million (95% CI, 0.000%-0.001%) following the second injection.In this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19-related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.
Post-translational modifications of soluble α-synuclein regulate the amplification of pathological α-synuclein
Authors: Shujing Zhang, Ruowei Zhu, Buyan Pan, Hong Xu, Modupe F. Olufemi, Ronald J. Gathagan, Yuanxi Li, Luyan Zhang, Jasmine Zhang, Wenxuan Xiang, Eliot Masahiro Kagan, Xingjun Cao, Chaoxing Yuan, Soo-Jung Kim, Christopher K. Williams, Shino Magaki, Harry V. Vinters, Hilal A. Lashuel, Benjamin A. Garcia, E. James Petersson, John Q. Trojanowski, Virginia M.-Y. Lee, Chao Peng
Journal: Nature Neuroscience (2023)
Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks
Authors: Hemanth Mohan, Xu An, X. Hermione Xu, Hideki Kondo, Shengli Zhao, Katherine S. Matho, Bor-Shuen Wang, Simon Musall, Partha Mitra, Z. Josh Huang
Journal: Nature Neuroscience (2023)
Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy
Authors: Daniel K. Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B. Williamson, Dennie T. Frederick, Tatyana Sharova, Michael G. White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan McCarthy, Carlos MoranSegura, Jane Messina, Kerry L. Thomas, Lancia Darville, Victoria Izumi, John M. Koomen, Shari A. Pilon-Thomas, Brian Ruffell, Vincent C. Luca, Robert S. Haltiwanger, Xuefeng Wang, Jennifer A. Wargo, Genevieve M. Boland, Eric K. Lau
Journal: Nature Cancer (2023)

Abstract Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of l -fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4 + T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and anti-programmed cell death protein 1 (PD1) responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity and, importantly, suggest that l -fucose is a powerful agent for safely increasing itICs and immunotherapy efficacy in melanoma.
Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice
Authors: C. P. Hedges, B. Shetty, S. C. Broome, C. MacRae, P. Koutsifeli, E. J. Buckels, C. MacIndoe, J. Boix, T. Tsiloulis, B. G. Matthews, S. Sinha, M. Arendse, J. K. Jaiswal, K. M. Mellor, A. J. R. Hickey, P. R. Shepherd, T. L. Merry
Journal: Nature Aging (2023)
Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models
Authors: Gonzalo Rodriguez-Berriguete, Marco Ranzani, Remko Prevo, Rathi Puliyadi, Nicole Machado, Hannah R. Bolland, Val Millar, Daniel Ebner, Marie Boursier, Aurora Cerutti, Alessandro Cicconi, Alessandro Galbiati, Diego Grande, Vera Grinkevich, Jayesh B. Majithiya, Desiree Piscitello, Eeson Rajendra, Martin L. Stockley, Simon J. Boulton, Ester M. Hammond, Robert A. Heald, Graeme C.M. Smith, Helen M.R. Robinson, Geoff S. Higgins
Journal: Clinical Cancer Research (2023)

DNA polymerase theta (Polθ, encoded by the POLQ gene) is a DNA repair enzyme critical for microhomology mediated end joining (MMEJ). Polθ has limited expression in normal tissues but is frequently overexpressed in cancer cells and, therefore, represents an ideal target for tumor-specific radiosensitization. In this study we evaluate whether targeting Polθ with novel small-molecule inhibitors is a feasible strategy to improve the efficacy of radiotherapy.
Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma
Authors: Abdullah A. Osman, Emre Arslan, Mason Bartels, Chieko Michikawa, Antje Lindemann, Katarzyna Tomczak, Wangjie Yu, Vlad Sandulache, Wencai Ma, Li Shen, Jing Wang, Anand K. Singh, Mitchell J. Frederick, Nakia D. Spencer, Jeffery Kovacs, Timothy Heffernan, William F. Symmans, Kunal Rai, Jeffrey N. Myers
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC. Experimental Design: Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 activation in vitro and in vivo on CDDP sensitivity and development of metastasis. Western blotting, immunostaining, whole-exome sequencing, single-cell transcriptomic and epigenomic profiling platforms were performed to dissect clonal evolution and molecular mechanisms. Results: Implantation of CDDP-resistant HNSCC cells into the tongues of nude mice resulted in a very high rate of distant metastases. The CDDP-resistant cells had significantly higher expression of NRF2 pathway genes in the presence of newly acquired KEAP1 mutations, or via epigenomic activation of target genes. Knockdown of NRF2 or restoration of the wild-type KEAP1 genes resensitized resistant cells to CDDP and decreased distant metastasis (DM). Finally, treatment with inhibitor of glutaminase-1, a NRF2 target gene, alleviated CDDP resistance. Conclusions: CDDP resistance and development of DM are associated with dysregulated and epigenetically reprogrammed KEAP1–NRF2 signaling pathway. A strategy targeting KEAP1/NRF2 pathway or glutamine metabolism deserves further clinical investigation in patients with CDDP-resistant head and neck tumors.
Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: L.E. Hendriks, K.M. Kerr, J. Menis, T.S. Mok, U. Nestle, A. Passaro, S. Peters, D. Planchard, E.F. Smit, B.J. Solomon, G. Veronesi, M. Reck
Journal: Annals of Oncology (2023)
2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis
Authors: Michelle M. Kittleson, Frederick L. Ruberg, Amrut V. Ambardekar, Thomas H. Brannagan, Richard K. Cheng, John O. Clarke, Laura M. Dember, Janell Grazzini Frantz, Ray E. Hershberger, Mathew S. Maurer, Jose Nativi-Nicolau, Vaishali Sanchorawala, Farooq H. Sheikh
Journal: Journal of the American College of Cardiology (2023)
Large-scale, national, family-based epidemiological study on<i>Helicobacter pylori</i>infection in China: the time to change practice for related disease prevention
Authors: Xian-Zhu Zhou, Nong-Hua Lyu, Hui-Yun Zhu, Quan-Cai Cai, Xiang-Yu Kong, Pei Xie, Li-Ya Zhou, Song-Ze Ding, Zhao-Shen Li, Yi-Qi Du
Journal: Gut (2023)

Background and aims Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. Methods From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. Results Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1–7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p&lt;0.05). Conclusion Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.
Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus
Authors: Eric F Morand, Gabriel Abreu, Richard A Furie, Vera Golder, Raj Tummala
Journal: Annals of the Rheumatic Diseases (2023)

In patients with systemic lupus erythematosus (SLE), lupus low disease activity state (LLDAS) attainment is associated with improved outcomes. We investigated LLDAS attainment in anifrolumab-treated patients.
Neurocognition, Behavior, Socioeconomic, and Health Outcomes of Pediatric Obstructive Sleep Apnea
Authors: Lena Xiao, Kanokkarn Sunkonkit, Jenny Shi, Indra Narang
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Neurocognition, Behavior, Socioeconomic, and Health Outcomes of Pediatric Obstructive Sleep Apnea." American Journal of Respiratory and Critical Care Medicine, 207(7), pp. 936–938
Annals Graphic Medicine - Dr. Mom: Assorted Clinical Pearls From 2022
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2023)

Web ExclusivesFebruary 2023Annals Graphic Medicine - Dr. Mom: Assorted Clinical Pearls From 2022FREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0081 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0020.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears quarterly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 24 January 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current IssueFebruary 2023Volume 176, Issue 2 ePublished: 24 January 2023 Issue Published: February 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians
Authors: Gerald Gartlehner, Andreea Dobrescu, Andrea Chapman, Ana Toromanova, Robert Emprechtinger, Emma Persad, Lisa Affengruber, Christoph Pieh, Irma Klerings, Gernot Wagner
Journal: Annals of Internal Medicine (2023)

Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD).